Decoding gut microbiome alterations in celiac disease: Implications for pathogenesis and treatment

Celiac disease (CD) is a chronic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals and characterized by intestinal inflammation, epithelial damage, and loss of immune tolerance. While a strict lifelong gluten-free diet (GFD) remains the cornerstone of treatment, accumulating evidence indicates that it does not consistently restore gut microbiome composition or function, and many patients experience persistent symptoms despite good dietary adherence. The gut microbiome has emerged as a key modulator of immune homeostasis, intestinal barrier integrity, and gluten metabolism, implicating microbial dysbiosis in both the initiation and progression of CD. Alterations in microbial composition and metabolic activity have been documented in genetically at-risk individuals prior to disease onset, in patients with active disease, and in treated patients on a GFD, suggesting a potential role of the microbiome in early pathogenesis, disease heterogeneity, and symptom persistence. In this review, we summarize current evidence on the bidirectional interactions between the gut microbiome and CD, including microbial-mediated gluten degradation, microbiome signatures associated with genetic susceptibility and disease activity, and the effects of a GFD on microbial ecology. We further discuss emerging strategies aimed at modulating the gut microbiome, including probiotics, prebiotics, postbiotics and precision probiotics, as potential adjunctive therapeutic approaches. A better understanding of microbiome-host interactions in CD may support the development of personalized therapeutic strategies that go beyond gluten avoidance and aim to restore microbial balance and immune regulation, thereby improving long-term outcomes.